Advice and Resources for the Biotech Industry

Advice and Resources for the Biotech Industry

Was it George W. Bush? His administration is best known for putting limits on the use of embryonic stem cells for research, for its continued support of space exploration (remember the proposal for the mission to Mars), and for questioning the science of global warming. This latter position contributed (at least in part) to the U.S. not supporting the Kyoto protocol to reduce greenhouse gas emissions. He did fulfill a commitment to doubling the NIH budget during the early years of his administration. Unfortunately, funding of the NIH became static at that point, and in inflation-adjusted dollars, is now about 20 percent lower than it was in 2003. George W. Bush also called for the doubling of certain research programs via the American Competitiveness Initiative, but Congress never funded it. His administration was repeatedly accused of being anti-science by adding politically correct appointees to various science panels, and for censoring reports that conflicted with his administrations views.

How about his father, George H.W. Bush? He took office in 1989 at a time of huge deficits, with the federal debt three times larger than it had been in 1980 (thanks to tax cutter Ronald Reagan). This severely handicapped his ability to influence national science policy. He advocated for increasing the scope of the U.S. space program, although budget issues prevented much from happening on this front. He also reauthorized the Clean Air act.

Could it possibly be Jeb Bush? As Governor of the State of Florida he obviously had much less ability to influence science than his Presidential father or brother. He did sign resolutions supporting tax incentives (as well as more funding) for the nations R&D programs. However, was also criticized when he was Governor for preventing scientists in Florida from even mentioning “global warming” or “climate change” in state reports.

Actually, none of these men come close to the individual that I think had the greatest and most lasting impact on American science: Vannevar Bush. He was one of those rare individuals who, when you read about what he did during his lifetime, leaves you stunned by the depth and breadth of his accomplishments.

Let me just give you a very brief summary of some of his achievements:

Professor of Electrical Engineering at MIT (later VP)Co-Founder of RaytheonDesigned and built the first digital integratorDeveloped and built the rapid selector, a machine for high speed location of information stored on microfilmCame up with the concept of the memex, a form of memory augmentation that was highly influential in the field of computer scienceDesigned and built the worlds most powerful (at that time) analog computer (differential analyzer)Director of the National Defense Research Committee and later the Office of Scientific Research and Development during WWII, where he was FDR’s science advisorInitiated and helped run the Manhattan Project, which allowed the U.S. to develop the atomic bomb during World War IIPresident, Carnegie Institute of WashingtonAuthor of numerous books, including Modern Arms and Free Men: A Discussion of the Role of Science in Preserving Democracy (1949)

He also wrote two of the most important and influential scientific essays ever published. He described a future where mankind could develop a way to access and manipulate accumulated knowledge in As We May Think for the Atlantic Monthly in 1945. Beyond that futuristic treatise, he authored Science: The Endless Frontier, a report to President Roosevelt on the best way to support and grow science in our country post-World War II.

The report, which led to the creation of the National Science Foundation, dates from July 1945, remains highly relevant. His words, on The Importance of Basic Research, from Science: The Endless Frontier:“Basic research is performed without thought of practical ends. It results in general knowledge and an understanding of nature and its laws. This general knowledge provides the means of answering a large number of important practical problems, though it may not give a complete specific answer to any one of them. The function of applied research is to provide such complete answers. The scientist doing basic research may not be at all interested in the practical applications of his work, yet the further progress of industrial development would eventually stagnate if basic scientific research were long neglected. One of the peculiarities of basic science is the variety of paths which lead to productive advance. Many of the most important discoveries have come as a result of experiments undertaken with very different purposes in mind. Statistically it is certain that important and highly useful discoveries will result from some fraction of the undertakings in basic science; but the results of any one particular investigation cannot be predicted with accuracy.

Basic research leads to new knowledge. It provides scientific capital. It creates the fund from which the practical applications of knowledge must be drawn. New products and new processes do not appear full-grown. They are founded on new principles and new conceptions, which in turn are painstakingly developed by research in the purest realms of science.

Today, it is truer than ever that basic research is the pacemaker of technological progress. In the nineteenth century, Yankee mechanical ingenuity, building largely upon the basic discoveries of European scientists, could greatly advance the technical arts. Now the situation is different.

A nation which depends upon others for its new basic scientific knowledge will be slow in its industrial progress and weak in its competitive position in world trade, regardless of its mechanical skill.”If you’re interested in learning more about this brilliant scientist, I’d highly recommend G. Pascal Zachary’s excellent biography Endless Frontier: Vannevar Bush, Engineer of the American Century.

Vannevar Bush’s view that we must continue to support and expand our basic scientific research programs is every bit as important today as it was in the past. Applied research (often referred to now as translational) has become the poster child for our nation’s biomedical research efforts, and there is no doubt that this initiative has great merit. However, there is a danger in forgetting the value of basic science. The current trend in drug discovery at Big Biopharma is to acquire promising, early stage drugs from other companies. The focus of the richest companies is on development, not research. A new company, Boston Pharmaceuticals, was just launched to execute on this exact business model. It was backed by a whopping $600 million investment from Gurnet, a healthcare investment fund.

In many quarters of biopharma, basic research has largely been kicked to the curb as being too expensive, a luxury that can no longer be afforded. However, if a majority of organizations see this as a winning strategy, where will the basic research get done? This opportunity, which some would label a burden, falls mostly on the shoulders of academia. Much of their focus is to uncover the basic foundations of how our world works. Academia, of course, has been the primary source of basic research in our country for decades. Unfortunately, there is a new trend in many research institutions that threatens to derail the ideals that Vannevar Bush championed. The new vogue: to re-direct the primary mission of the university, and to change the focus of the professors employed therein along a business path.

In Wisconsin, Gov. Scott Walker, when he isn’t trying to break the states’ unions, attempted to change the basic charter of the University of Wisconsin away from a “search for truth” and efforts to “improve the human condition” to instead focus on meeting “the states workforce needs.” This effort, thankfully, was blocked [disclosure: I am a graduate of the U. of Wisconsin]. An increased focus on business applications has also been spreading among the nation’s universities. Michael Young, former President of the University of Utah, the University of Washington, and now head of Texas A&M, is primarily known for his efforts to facilitate the spinning out of companies based on intellectual property created by the universities. Many other university leaders seek to follow down this path.

Let me be clear: there’s nothing wrong with encouraging those faculty members who have an entrepreneurial spirit to help set up a company to commercialize their work. Those who want to head in that direction should bend over backwards to make sure that their students and post-docs don’t wind up being exploited by having them work on commercial projects that may not allow them to publish or publicly share the fruits of their labors. However, it’s a bad idea to push those who have no interest in the commercialization pathway down that route, or to use this against them in tenure decisions.

Basic research in biology continues to provide novel insights in many areas, many of which have indeed been pushed forward into commercial applications. Example: the CRISPR system is thought to have evolved as a form of immune system in bacteria, providing resistance to foreign DNA elements that can invade and kill them. The early research on the functional role of CRISPR and how bacteria defend themselves against viruses did not immediately suggest a utility in treating human diseases. Eventually, clever scientists adapted this system to develop a method that allows users to alter specific DNA sequences in living animals. It holds tremendous promise for use in treating a large number of rare diseases as well as cancer. As a result, a number of biotech companies have been formed around the concept, and patents covering the technology are the subjects of a fierce legal battle. Without grants supporting the basic research that was done here, practical applications would not now be in the works.

Politicians should be excluded from the grant approval process. One can easily imagine the negative outcome had their been congressional hearings on the value of this early work, with scientists involved in the basic research being grilled on future unknown practical applications of bacterial immune systems. As Sean Carroll, a theoretical physicist at Cal Tech, described it, “It is not only that politicians are making fun of scientific projects that sound outlandish or impractical, they are literally rejecting science in order to gain political advantage.” Equally concerning is legislation introduced by Senators Ted Cruz (R-Texas) and Mike Lee (R-Utah) known as the RESULT Act. It would, in part, give politicians the ability to override FDA decisions on approving or rejecting drugs. This is a terrible idea that’s been put forth by people who are normally antithetical to increasing the role of government in people’s lives.

Many people are concerned about the downgrading of basic research in our country. MIT faculty members recently authored a report on the subject “The Future Postponed: Why Declining Investment in Basic Research Threatens a U.S. Innovation Deficit.” Even with the unfettered ability to choose their own research projects, many scientists complain that the current grant system is biased against cutting edge work in favor of “play-it-safe” approaches that are likelier to get funded. This concern has been raised for years with only minor changes to the system.

Here in Seattle, Microsoft co-founder Paul Allen has been channeling the spirit of Vannevar Bush. In addition to creating an Institute for Brain Science in 2003 (total commitment to date: $500 million), he also started an Institute for Cell Science (another $100 million investment) in 2014. The institutes run on the principle of open science. Data produced by the scientists at each of these organizations is freely shared with anyone who is interested, and is considered a tremendous resource by the scientific community. Mr. Allen has just announced the funding of a new Frontiers initiative, which will be part of his Cell Sciences Institute. Its goal is to use an integrative (i.e. multi-disciplinary) approach to take on difficult, risky problems that would otherwise be considered unfundable by more convectional groups. It’s meant to be a high risk, high reward endeavor focused on transformational changes. He clearly understands that without some commitment to basic, exploratory science, applied research, such as that done by the Big Biopharma companies, will eventually grind to a halt. A side benefit of his largess is providing jobs for area scientists previously laid off by biotech companies that were either acquired, or cut back significantly on their R&D efforts. Philanthropist Sean Parker (of Napster and Facebook fame) just announced a $250 million unconventional initiative in setting up an immunotherapy-focused consortium to focused on cancer biology. I’m hoping that other members of the Forbes billionaire list will embrace the spirit of Vannevar Bush and emulate the financial support provided by Paul Allen and Sean Parker. Put simply, basic research is the foundation upon which innovation is built.

Follow me on Twitter @lymanbiopharma to ensure you don't miss any of my blog posts!